Kuwanon T and Sanggenon a Isolated from Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells.

We previously investigated the methanolic extract of bark and characterized 11 compounds from the extract: kuwanon G (), kuwanon E (), kuwanon T (), sanggenon A (), sanggenon M (), sanggenol A (), mulberofuran B (), mulberofuran G (), moracin M (), moracin O (), and norartocarpanone (). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them, and markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with and inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with and , suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together, and are potential candidates for developing therapeutic and preventive agents for inflammatory diseases.